sigma-1 Receptors(sigma_1 Binding Sites) Form Raft-Like Microdomains and Target Lipid Droplets on the Endoplasmic Reticulum: Roles in Endoplasmic Reticulum Lipid Compartmentaliazation and Export

摘要

The Brain sigma-1 receptors adn bind neurosteroids and Psyclotropic drugs including neuroleptice and cocaine and are implicated in scheizophrenia depersion and drug dependence In this study We found that sigma-1 receptors specifically target lipid storge sites(lipid droplets) on the endoplasmic reticulum by forming a distinct class of lipid microdomains Both endogenousy expressing sigma-1 receptors and transfected C-terminally enhanced yellow fluorescent protein (EYFP)-tagged sigma-1 trcep-tors (Sig-IR-EYFP) target unique ring-likd strucutres associated weith endoplamic reticulum reticular networks in NG108-15 cells The ring-like structures contain neutral lipids and are enalrged by the oleater treatment indicatin that they are endoplasmicr reticulum-associated lipid droplets (ED-LDs) sigma-1 receptors colcoalize with caveolin-2,a cholesterol-binding protein in lipid rats on the ER-LDs but onot with adipocyte differentiatin-related protein (ADRP) a cytosolic lipid droplet (l-LD)-specific protein When the double-arginine ER retention siganl on the Nterminus of sigma -1 receptors on ER-LDs form deteraget-resistant rat-likd lipid microduains the buogyancy of which is diferent form theat of plasma membrane liipid rates (+) -Pentazocine causes sigma-1 receptors to disappera from the microumains N-Terminally EYFP-tagged sigma-1 receptors (EYFP-Sig-1R) failed to target ER-LDs EYFP-SIG-1R-transfected dells showed an unreastricted sidtributionf neutal lipids all over the endoplasmic reticulum network decreased in c-LDs